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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 415 records · Page 23Linked to original sources

[Pathologic reconsideration on allergic bronchopulmonary aspergillosis and mycosis].

We examined lung specimens that fulfilled the pathological criteria of Bosken and were obtained from 5, patients with allergic bronchopulmonary aspergillosis/mycosis (ABPA/M). A finding common to all 5 was the presence of hard mucous plugs containing numerous eosinophils and fungal hyphae in the bronchi, showing central bronchiectasis. Bronchocentric granulmatosis with tissue eosinophilia (4 cases), xanthogranulomatous lesions (3 cases), eosinohilic pneumonia (2 cases) and organizing pneumonia (3 cases) were recognized only in bronchi distal to the mucous plugs (BMP). Almost normal lung parenchyma could be seen in some areas distal to the BMP. We found clusters of degenerated eosinophils (CDE) showing a "fir-tree like structure" and fungal hyphae in both the mucous plugs and the peripheral lesions. Most CDEs were free in the exudate and were not engulfed by macrophages. The presence of fungi in the mucous plugs may have caused marked inflammation in the wall around the BMP, which may have made the walls fragile and caused central bronchiectasis. The fungi in the mucous plugs may have caused the peripheral lesions via aerogenous dissemination. For this reason, we conclude that ABPA/M is an infectious disease, and that the primary lesion in ABPA/M is the formation of mucous plugs. Therefore, the presence of mucous plugs containing fungi and many eosinophils is diagnostic of ABPA/M.

Aged↗

Immunoconfocal localization of gelatinase B expressed by migrating intrastromal epithelial cells after deep annular excimer keratectomy.

PURPOSE: Intrastromal epithelial migration occurs following deep excimer annular keratectomy. Our purpose is to determine the localization of gelatinase B expression and its relationship to migrating intrastromal epithelial cells following deep annular excimer keratectomy. METHODS: Rabbit corneas were treated with deep annular ablation and harvested 3, 5, 7 and 14 days following surgery. Histological examination was performed. Confocal microscopy was used to determine the time and the pattern of gelatinase B expression. This was compared to AE-5, vimentin, and alpha-smooth muscle actin immunolocalization. RESULTS: Histologic examination revealed islands of epithelial cells within the corneal stroma after deep annular excimer ablation, whereas eyes treated with superficial annular keratectomy did not show intrastromal epithelial migration. Immunoconfocal microscopy using monoclonal anti-matrix metalloproteinase-9 (MMP-9) antibody demonstrated the presence of gelatinase B at the outer borders of the intrastromal epithelial islands following deep annular excimer keratectomy. CONCLUSION: Gelatinase B may be involved in the process of intrastromal epithelial migration following deep annular excimer keratectomy.

Actins↗

Prediction of catalepsies induced by amiodarone, aprindine and procaine: similarity in conformation of diethylaminoethyl side chain.

Recently, clinical cases of parkinsonism due to antiarrhythmics drugs amiodarone and aprindine and a local anesthetic drug procaine have been reported. We performed both in vivo and in vitro experiments to quantitatively predict the intensity of catalepsy by these drugs and haloperidol in mice. Haloperidol showed the most potent relative intensity of catalepsy, followed by aprindine, metoclopramide, tiapride, amiodarone and procaine, in that order. In vivo dopamine D1 and D2 receptor occupancies of the six drugs to the striatum were observed. In vitro binding affinity (Ki) of these drugs to the D1 and D2 receptors in the striatum synaptic membrane was within the range of 60 nM to 706 microM, 0.5 nM to 75 microM and 860 nM to 115 microM, respectively. A good correlation between the relative intensity of drug-induced catalepsy and the Ki values for the dopamine D1 and D2 receptors was obtained (r =.911 and r =.896, respectively; P <.05). The partial tertiary structure of the tested drugs was well superimposed on that of haloperidol. In conclusion, these drug-induced catalepsies were due to the blockade of the D1 and D2 receptors, which was related to the analogous tertiary structures (diethylaminoethyl side chain).

Amiodarone↗

[A case of stage IV breast cancer showing long-term complete response to combination therapy with 5'-DFUR and MPA].

We report a 62-year-old woman with supraclavicular lymph node, pleural and bone metastases from breast cancer showing a long-term complete response to combination therapy with 5'-DFUR and MPA. A large amount of pleural effusion was drained followed by administration of ADM, which improved the amount of effusion. Treatment with CAF and TAM decreased tumor size, but CAF was abandoned due to severe leukopenia. Mastectomy was performed for local control. However, levels of tumor markers increased progressively. Administration of CMF was tried, but tumor markers continued to increase. Therefore, combined chemoendocrine therapy with 5'-DFUR and MPA was undertaken. Levels of tumor markers normalized and a complete response was obtained 13 months after starting this combination therapy. There are no further metastatic lesions evident, and this status has been consistently maintained for more than three years (six years and five months after diagnosis of breast cancer). There were no significant side effects of this combination therapy except for mild weight gain and moon face. This combination regimen with 5'-DFUR and MPA is considered useful as a second-line treatment for advanced breast cancer.

Adenocarcinoma, Scirrhous↗

[Terminal care of the cancer patient at home--patient and family spending the last moments together].

Some 129 cancer patients were taken care of at home by the visiting nurse team of our hospital since 1994 to 1997; 116 patients have already died, 50 of them at home (group A), and 66 at the hospital (group B). We analyze the differences the between two groups in nutritional assistance, pain control and manpower in looking after a patient. Twice as many patients in group A took nutritional medication (drip infusion or intravenous hyperalimentation, for example) than group B. More patients in group A used oral and suppository morphine than group B. In group A 70% of patients (56% in group B) had more than two persons looking after at home. The important factors for a good recuperation at home are: 1. Available nutritional assist available. 2. Good control. 3. Less burden and anxiety of the person looked after. To spend pain desirable last moments together, it is important for the visiting nurse team to take proper care and to confirm the wishes of the patient and family, considering the rapidly changing conditions of the individual patient.

Aged↗

Amino acids and peptides. XXXII: A bifunctional poly(ethylene glycol) hybrid of fibronectin-related peptides.

An amino acid type poly(ethylene glycol) (aaPPEG) was prepared and its application to a drug carrier was examined. The peptides, Arg-Gly-Asp (RGD) and Glu-Ile-Leu-Asp-Val (EILDV) which were reported as active fragments of Fibronectin (a cell adhesion protein), were conjugated with aaPEG (molecular weight, 10,000). The hybrid, RGD-aaPEG-EILDV, was prepared by a combination of the solid-phase method and the solution method. Antiadhesive activity of the peptides was not lost by its hybrid formation with the large aaPEG molecule. A mixture of RGD (0.43 mmol) and EILDV (0.43 mmol) did not demonstrate an antiadhesive effect, but the hybrid containing 0.43 mmol of each peptide did exhibit this effect.

Carrier Proteins↗

A Case of Apocrine Carcinoma of the Breast Presenting as Two Cysts.

A case of apocrine carcinoma of the breast presenting as two cysts is reported. A 60-year-old woman had two soft, mobile, well-defined masses measuring 4 x 2.5 cm and 1.5 x2.5 cm in diameter in the lower-inner quadrant of the right breast. Tumor markers such as CEA, CA15-3, BCA225 and NCC-ST-439 were within normal limits. Mammography showed two oval radioopaque masses with microcalcificatin in the smaller one. Ultrasonography disclosed two cysts and papillary projection in the larger one. Fine needle aspiration cytology revealed apocrine carcinoma of the breast. Excisional biopsy confirmed the diagnosis of apocrine carcinoma with focal invasion. Modified radical mastectomy was performed. Pathological study showed that the tumor mainly proliferated in the cysts and the two cysts communicated with each other through an involved duct. There was no apocrine metaplasia in adjacent mammary gland. There were no metastatic lymph nodes. This case may be regarded as intraductal apocrine carcinoma developing two cysts with focal invasion.

Journal Article↗

Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2. Segregate expression profiles from a rap1GAP gene product.

Mouse Spa-1 gene with a region homologous to the human rap1GAP gene is transcriptionally induced in the lymphocytes by mitogenic stimulation. Herein we have cloned a cDNA for its human counterpart. SPA-1 cDNA encodes a 130-kDa protein (p130(SPA-1)) consisting of proline-rich regions and rap1GAP-related domain followed by a coiled-coil stretch. Baculovirally expressed p130(SPA-1) exhibited GTPase-activating protein (GAP) activity for Rap1 and Rap2, but not for Ras, Rho, Cdc42, Rac, and Ran, with comparable specific activity to the rap1GAP gene product (p85/95(rap1GAP)). In the cells, p130(SPA-1) was mostly localized at the perinuclear membranous region co-localizing with Rap1 and Rap2. Expression of SPA-1 and rap1GAP genes tended to be segregate in various tissues, lymphoid tissues expressing abundant SPA-1 transcript without rap1GAP, while those such as brain, kidney, and pancreas exhibiting rap1GAP mRNA with little SPA-1. Promyelocytic HL-60 cells, which expressed p130(SPA-1) with little p85/95(rap1GAP) in uninduced state, showed progressive decline in p130(SPA-1) and conversely drastic increase in p85/95(rap1GAP) as they ceased from proliferation and differentiated into macrophages by 12-O-tetradecanoylphorbol-13-acetate. These results suggested that products of SPA-1 and rap1GAP genes, albeit comparable GAP activity for Rap1 and Rap2, functioned in the distinct contexts depending on cell types and/or states.

Amino Acid Sequence↗

Activation of the mitogen-activated protein kinase ERK2 by the chemoattractant folic acid in Dictyostelium.

The Dictyostelium MAP kinase ERK2 is activated by extracellular cAMP in aggregation-competent cells and is required for receptor activation of adenylyl cyclase (Maeda, M., Aubry, L., Insall, R., Gaskins, C., Devreotes, P. N., and Firtel, R. A. (1996) J. Biol. Chem. 271, 3351-3354; Segall, J., Kuspa, A., Shaulsky, G., Ecke, M., Maeda, M., Gaskins, C., Firtel, R., and Loomis, W. (1995) J. Cell Biol. 128, 405-413). This cAMP-dependent activation of ERK2 is mediated by the serpentine, G protein-coupled cAMP receptors. However, ERK2 activation by cAMP is at least partially heterotrimeric G protein-independent, with a level of activation in cells lacking the sole Gbeta subunit or the G protein-coupled cAMP receptors-coupled Galpha2 subunit that is approximately 50% that of wild-type cells (Maeda, M., Aubry, L., Insall, R., Gaskins, C., Devreotes, P. N., and Firtel, R. A. (1996) J. Biol. Chem. 271, 3351-3354; Segall, J., Kuspa, A., Shaulsky, G., Ecke, M., Maeda, M., Gaskins, C., Firtel, R., and Loomis, W. (1995) J. Cell Biol. 128, 405-413). Folic acid, a chemoattractant in the vegetative cells that enables amoebae to find bacteria in the wild, also triggers the activation of adenylyl cyclase, which is impaired in the vegetative cells lacking the Galpha protein subunit Galpha4 (Hadwiger, J., Lee, S., and Firtel, R. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10566-10570). In this study, we show that folic acid activates ERK2 in developmentally regulated manner and is required for ERK2 stimulation of adenylyl cyclase activity. Maximum levels of folate-stimulated ERK2 activity occur in cells from very early in development, prior to aggregation, and again at the tipped aggregate stages, corresponding to the stages in which folate receptors and the coupled Galpha subunit Galpha4 are maximally expressed. During the activation by folic acid, ERK2 is phosphorylated on tyrosine residue(s) and contemporaneously shows a mobility shift on SDS-PAGE. Interestingly, this activation is not elicited in the absence of Gbeta subunits, in contrast to the response to cAMP. This response also requires the Galpha4 subunit known to be required for other folic acid-mediated responses (Hadwiger, J., Lee, S., and Firtel, R. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10566-10570). Furthermore, we show that the activation of ERK2 by cAMP is independent of the Galpha4 subunit, while the activation of ERK2 by folate is independent of Galpha2. Taken together, these data indicate that there are at least two pathways of ERK2 activation, heterotrimeric G protein-dependent and -independent pathways.

Adenylyl Cyclases↗

GATA-6 DNA binding protein expressed in human gastric adenocarcinoma MKN45 cells.

A cDNA for the GATA-6 (GATA-GT1) DNA binding protein was cloned from a library of the human gastric adenocarcinoma cell line MKN45. The deduced amino acid sequence (449 residues) indicates that the primary structure of human GATA-6 is highly homologous to that of the rat protein. The potential phosphorylation site for protein kinases (A and C), and histidine and alanine clusters are conserved. Whereas the rat H+/K+-ATPase alpha and beta subunit genes have two and three GATA protein binding sites in their promoter regions, respectively, the human alpha subunit gene has only one binding site [Maeda, M., Kubo, K., Nishi, T. and Futai, M. (1996) J. Exp. Biol. 199, 513-520]. We cloned the 5'-upstream region of the human H+/K+-ATPase beta subunit gene by genome walking and found that it also has a single GATA protein binding site near the TATA box. The GATA sites of the human alpha and beta subunit genes are recognized by the zinc finger domain of human GATA-6. The conservation of the GATA protein binding sites suggests that they are important for the gene regulation of the human and rat H+/K+-ATPase.

Adenocarcinoma↗

Amino acid residues responsible for galactose recognition in yeast Gal2 transporter.

A novel, systematic approach was used to identify amino acid residues responsible for substrate recognition in the transmembrane 10 region of the Gal2 galactose transporter of Saccharomyces cerevisiae. A mixture of approximately 25,000 distinct plasmids that encode all the combinations of 12 amino acids in transmembrane 10 that are different in Gal2 and the homologous glucose transporter Hxt2 was synthesized. Selection of galactose transport-positive clones on galactose limited agar plates yielded 19 clones, all of which contained the Tyr446 residue found in Gal2. 14 of the 19 clones contained Trp455 found in Gal2, whereas the other 5 contained Cys455, a residue not found in either Gal2 or Hxt2. When Tyr446 of Gal2 was replaced with any of the other 19 amino acids, no galactose transport activity was observed in the resulting transporters, indicating that Tyr446 plays an essential role in the transport of this sugar. Replacement of 2 amino acids of Hxt2 with the corresponding Tyr446 and Trp455 of Gal2 allowed the modified Hxt2 to transport galactose. The Km of galactose transport for the modified transporter was 8-fold higher than that of Gal2. These results and other evidence unequivocally show that Tyr446 is essential and Trp455 is important for the discrimination of galactose versus glucose.

Amino Acid Sequence↗

Integrin alpha6 is involved in follicular growth in mice.

We previously reported that integrin alpha6 is expressed on granulosa cells in the inner layers of the human and porcine ovarian follicles, where granulosa cells have no direct contact with basal lamina. In this study, we examined the physiological role of integrin alpha6 on follicular growth with an immature superovulated mice model using the anti-integrin alpha6 monoclonal antibody, GoH3. In the ovaries of 9- to 20-day-old mice, integrin alpha6 was detected on all the layers of granulosa cells in the primordial, primary, and secondary follicles by immunohistochemistry. The 13-day-old female mice were superovulated by pregnant mare serum gonadotropin and human chorionic gonadotropin with the treatment of intraperitoneal administration of GoH3, or a control antibody, or PBS. In the group of GoH3 treatment, successful ovulation was observed in 57+/-25.7% of the animals, whereas no ovulation was observed in the control groups (p<0.01). These findings indicate that integrin alpha6 is involved in gonadotropin-induced follicular growth.

Animals↗

Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent exocytotic machinery.

Doc2 has two C2 domains that interact with Ca2+ and phospholipid. Munc13 has two C2 domains and one C1 domain that interacts with phorbol ester or diacylglycerol (DAG) and phospholipid. Both Doc2 and Munc13 are implicated in Ca2+-dependent neurotransmitter release, but their modes of action still remain unclear. We show here that Doc2 interacts with Munc13 both in a cell-free system and in intact PC12 cells during the high K+-induced Ca2+-dependent exocytosis. The Doc2-Munc13 interactions are stimulated by phorbol ester through the C1 domain of Munc13. Overexpression of the Doc2-interacting domain of Munc13 reduces the Ca2+-dependent exocytosis from PC12 cells, and co-expression with Doc2 suppresses this reduction. These results, together with the earlier findings that secretagogues produce DAG and elevate cytoplasmic Ca2+, suggest that the DAG-induced Doc2-Munc13 interactions play an important role in Ca2+-dependent exocytotic machinery.

Animals↗

Cerebral extracellular lactate concentration and blood flow during chemical stimulation of the nucleus tractus solitarii in anesthetized rats.

The extracellular lactate concentration and blood flow in the cerebral cortex of urethane-anesthetized, paralyzed and artificially ventilated rats were monitored continuously and simultaneously using an enzyme electrode and a laser Doppler flowmeter (LDF), respectively, during chemical stimulation of the nucleus tractus solitarii (NTS) by microinjection of L-glutamate (1.7 nmol 50 nl). Chemical stimulation of the NTS significantly decreased the arterial blood pressure (ABP) from 85 +/- 17 to 68 +/- 14 mmHg, heart rate from 418 +/- 13 to 402 +/- 19 beats x min(-1) and cerebral blood flow (CBF) by 17.9 +/- 6.2% (P < 0.001). However, chemical stimulation of the NTS significantly increased the lactate concentration by 58.9 +/- 17.3 microM (P < 0.001). Barostat maneuver, which held systemic ABP constant during chemical stimulation of the NTS attenuated the responses in CBF and lactate concentration by 30 and 27%, respectively. The onset of the increase in lactate concentration was delayed about 19 s after that of the CBF decrease. Circulatory lactate produced no significant change in the cerebral extracellular lactate concentration. These results indicate that chemical stimulation of the NTS induces an increase in extracellular lactate concentration in the cerebral cortex through a decrease in CBF via cerebral vasoconstriction.

Animals↗